To characterize these invisible colonizers, known en masse as the “human microbiome,” scientists with the Human Microbiome Project Consortium collected tissue samples from 242 healthy American volunteers from several different locations on their bodies.
These sites, or microbial “habitats,” ranged from the nasal and oral passages to the skin, the vagina and feces.
Researchers found that the number and variety of microbes differed among an individual’s body habitats. They also observed that conditions such as temperature and acidity, as well as the work being done by the human cells in the various habitats, appear to influence which microbes live there.
For example, there are roughly 4,000 species of bacteria in the intestine, where they help digest nutrients and produce vitamins and anti-inflammatory compounds. On the other hand, the vagina has only about 300 — and the diversity decreases during pregnancy to provide a healthy passage for the infant.
The researchers found that, as a rule, the microbial inhabitants of body habitats are similar from person to person. The bigger differences are between what lives in any individual’s habitats. One person’s skin and tongue are far more different from each other than are those of two people.
“There are more similarities between creatures that survive in two different deserts than between [those that live in] a desert or a rain forest,” said Harvard computational biologist Curtis Huttenhower, lead co-author of a study published Wednesday in the journal Nature. “The different regions of your body are these bugs’ deserts and rain forests.”
While humans are home to viruses and fungi, the vast majority of the microbial fellow-travelers are bacteria. Bacterial cells outnumber human cells 10 to 1. Their genes outnumber human genes by a factor of hundreds.
Using DNA sequencing technology, which has become dramatically faster and cheaper over the past decade, the researchers estimated the presence of more than 10,000 distinct microbial species in healthy humans. They also developed computational methods that allowed them to analyze millions of microbes’ genes one by one. That part of the project was led by Mihai Pop of the University of Maryland.
Huttenhower said, “DNA sequencing is our new microscope. Now that we have this genetic data, we can turn the dial and focus on microbes in a new, computational way.”
In their analysis, the researchers found that what matters in the different body habitats is the work needing to be done rather than what microbes are doing it. In the intestine, for example, one important job for microbes is breaking down certain carbohydrates in food. It turns out that the specific microbes doing that work can differ somewhat among people and can even change in a single person over time.
James M. Anderson, an NIH scientist who helped oversee the project, said that observation could be of use in treating some diseases, especially ones of the intestinal tract. “There is not a strict profile of bugs,” he said. “But what is gratifying is that even if you come across a microbial ‘profile’ you have not seen before, you will know its function. And that has practical, medical use.”
Lita M. Proctor, the project’s director at the NIH, noted that there is already such a treatment in use. Sometimes people with the hospital-acquired infection Clostridium difficile enteritis receive transplants of feces from healthy individuals to regenerate their intestinal microbiomes.
But Stanford University researcher David Relman said the fact that a person’s microbiome can change over time makes it hard to tell whether a microbial community is causing, worsening or, maybe, alleviating a disease.
“It turns out that time is as important to explain microbial variation as is space,” said Relman, who was not involved in the project. “Time is especially important when you are developing as a child or when you have experienced a major disturbing force” to your health.
He said the consortium researchers should have collected microbe samples for far longer than the 22-month window they used. It will be important to examine people’s microbiomes for longer periods to gain understanding of how they vary with age, diet, residence and factors not emphasized in the studies.
The new microbiome research appeared Wednesday in two papers in the journal Nature and 14 papers in the Public Library of Science. It is the culmination of a five-year collaboration of over 200 members from about 80 institutions worldwide. The NIH provided $173 million for the research.
“There were groups generating data, performing microbiology, thinking about computation, managing all of the scientists and reaching out to the communities,” Huttenhower said. “It takes a village to finish science these days.”